Pharmacological Strategies for Targeting Residual Symptoms in Depression

Achieving full symptom remission in major depressive disorder (MDD) should be the ultimate objective in the treatment of depressed patients. However, antidepressant monotherapies have shown to have limited efficacy in the treatment of MDD, as evidenced by the relatively high rate of residual symptoms even among responders to antidepressant treatments. These symptoms, which include anxiety, irritability, insomnia, somnolence/fatigue, apathy, and cognitive and executive dysfunction, are associated with an increased risk of relapse and poor psychosocial functioning. Comprehensive clinical data are not yet available to guide management of these symptoms—whether residual or drug-related—in patients treated pharmacologically for depressive disorders. Suggested approaches to the management of residual symptoms include addressing treatment-emergent side effects and comorbid conditions, optimizing antidepressant dosing, and using augmentation therapies. In this chapter, we will review how best to assess residual symptoms and some of the preferred pharmacological strategies to address them.